GABA Effects of Nicotine in Men and Women

描述(由申请人提供)：尼古丁已被证明影响大脑中的GABA能功能。在大鼠中，尼古丁急剧增加GABA的释放，人类和动物研究表明GABA能系统与尼古丁成瘾的获得和维持有关。在人类的初步研究中，用尼古丁注射的磁共振波谱(MRS)观察到人类皮质GABA水平的一过性增加。此外，尼古丁已经被发现可以使大脑中GABA的合成增加2-4倍。了解急性尼古丁给药对大脑GABA的影响可能有助于深入了解吸烟与常见疾病的相互作用，这些疾病已知涉及GABA能系统，如抑郁症和酒精中毒。这个项目还可能提供进一步的信息，说明为什么有些人很难戒烟。已经证明，与月经周期有关的大脑GABA水平的变化会因吸烟而取消，而且男性和女性对尼古丁的反应有所不同，因此该项目还将探索人脑中GABA能反应的性别差异。以下几个问题将得到解答：1)急性服用尼古丁是否会增加大脑中的GABA？2)大脑中的GABA需要多长时间才能恢复到尼古丁之前的水平？3)尼古丁是否会增加GABA的合成？4)性别是否会影响尼古丁引起的大脑中GABA水平和合成速率的变化？将对40名健康吸烟者(男性20名，女性20名)在戒烟一夜后大脑GABA的浓度和合成率进行测量。测量将进行两次，一次使用尼古丁吸入器，一次使用安慰剂吸入器。排除标准将包括目前的神经精神障碍或最近的此类病史。公共卫生相关性：这项工作将确定大脑皮层GABA能神经元的变化与尼古丁以及人们对尼古丁的一些主观感受有关。这一结果可能有助于解释为什么一些较新的药物戒烟方法是有效的，并指导新方法的开发。这一结果也可能有助于我们理解为什么抑郁症患者和酒精依赖患者更有可能对烟草上瘾。

DESCRIPTION (provided by applicant): Nicotine has been shown to affect GABAergic function in the brain. In rats, nicotine increases GABA release acutely, and human and animal studies have implicated the GABAergic system in the acquisition and maintenance of nicotine addiction. Transient increases in levels of human cortical GABA levels have been observed by magnetic resonance spectroscopy (MRS) with nicotine administration in preliminary studies in humans. Furthermore, nicotine has been seen to elevate brain GABA synthesis 2-4 fold in human brain. Knowing the effects of acute nicotine administration on brain GABA may provide insight into the interaction of tobacco smoking with prevalent disorders that are known to involve the GABAergic system, such as depression and alcoholism. This project may also provide further information about why it is so hard for some people to stop smoking. It has been shown that menstrual cycle related changes in brain GABA levels are abolished by smoking, and that men and women have some different responses to nicotine, so this project will also explore gender-based differences in GABAergic responses in the human brain. Several questions will be answered: 1) Does acute nicotine administration increase brain GABA? 2) How long does it take brain GABA to return to pre-nicotine levels? 3) Does nicotine increase GABA synthesis? 4) Does gender affect nicotine-induced changes in brain GABA levels and rates of synthesis? The concentration and rates of synthesis of brain GABA will be measured in 40 healthy smokers (20 men, 20 women) after overnight abstinence from smoking. The measurements will be conducted twice, once with a nicotine inhaler, and once with a placebo inhaler. Exclusion criteria will include current neuropsychiatric disorders, or a recent history of such. PUBLIC HEALTH RELEVANCE: This work will establish what changes in GABAergic neurons in the cerebral cortex are associated with nicotine and some of the subjective feelings that people experience with nicotine. The outcomes may help to explain why some of the newer drug-based smoking cessation approaches are effective and guide the development of new approaches. The results may also contribute to our understanding of why depressed people and patients with alcohol dependence have a greater likelihood of addiction to tobacco.